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Cell Stem Cell. 2014 Jul 3;15(1):102-10. doi: 10.1016/j.stem.2014.04.019. Epub 2014 May 15.

MBD3/NuRD facilitates induction of pluripotency in a context-dependent manner.

Author information

1
Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Doctoral Programme in Experimental Biology and Biomedicine, Centre for Neuroscience and Cell Biology and Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal.
2
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh BioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, UK.
3
Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
4
Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. Electronic address: jcs64@cscr.cam.ac.uk.

Abstract

The Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for embryonic development and pluripotent stem cell differentiation. In this study, we investigated whether NuRD is also involved in the reverse biological process of induction of pluripotency in neural stem cells. By knocking out MBD3, an essential scaffold subunit of the NuRD complex, at different time points in reprogramming, we found that efficient formation of reprogramming intermediates and induced pluripotent stem cells from neural stem cells requires NuRD activity. We also show that reprogramming of epiblast-derived stem cells to naive pluripotency requires NuRD complex function and that increased MBD3/NuRD levels can enhance reprogramming efficiency when coexpressed with the reprogramming factor NANOG. Our results therefore show that the MBD3/NuRD complex plays a key role in reprogramming in certain contexts and that a chromatin complex required for cell differentiation can also promote reversion back to a naive pluripotent cell state.

PMID:
24835571
PMCID:
PMC4082719
DOI:
10.1016/j.stem.2014.04.019
[Indexed for MEDLINE]
Free PMC Article

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